tbuckley/cabot-search huggingface dataset:
Abstract 11733: Racial Disparities in Cardiometabolic Risk Factors Among Pregnant Women in the United States
Authors: Maya Farhat, Sana Rabeeah, Sadeer Al-Kindi
Journal: Circulation (2022)

Background: Pregnancy-related mortality has notably increased in the United States over the past 3 decades, with cardiovascular disease as the leading cause of mortality post-partum. Significant racial disparities have been noted in pregnancy-related mortality in the US. We sought to study contemporary trends and disparities in cardiometabolic risk factors (CMRFs) among pregnant women in the US. Methods: We used the 2016-2020 natality database maintained by the CDC. We identified pregnant women with first live birth and known self-reported race (Black vs White). We explored overall prevalence (aggregated 2016-2020) and relative changes (between 2016 and 2020) in CMRFs: pre-pregnancy diabetes (Pre-DM), gestational diabetes (G-DM), pre-pregnancy hypertension (Pre-HTN), gestational hypertension (G-HTN), smoking, and obesity. Results: A total of 3,141,830 pregnancies in White women and 436,895 pregnancies in Black women were noted. Overall, Black mothers had higher rates of Pre-DM, Pre-HTN, G-HTN, and obesity, but lower rates of smoking and G-DM. From 2016-2020, there were significant increases in all CMRFs, except smoking, which decreased. There was a more significant increase in Pre-DM and G-HTN in Black mothers, while there were more significant increases in Pre-HTN and obesity in White mothers. A 15% relative increase in the prevalence of any CMRF was seen in both races. Conclusions: In this large analysis of pregnant mothers in the US, cardiometabolic risk factors were present in 35% of White mothers and 43% of Black mothers, with significant increases from 2016 to 2020 in both races. Future studies should focus on identifying mechanisms of the observed associations.
Faecal Microbiota transplantation affects liver DNA methylation in Non-alcoholic fatty liver disease: a multi-omics approach
Authors: Daniela Stols-Gonçalves, Anne Linde Mak, Mette S. Madsen, Eduard W. J. van der Vossen, Eveline Bruinstroop, Peter Henneman, Femke Mol, Torsten P. M. Scheithauer, Loek Smits, Julia Witjes, Abraham Stijn Meijnikman, Joanne Verheij, Max Nieuwdorp, Adriaan G. Holleboom, Evgeni Levin
Journal: Gut Microbes (2023)

Individuals with nonalcoholic fatty liver disease (NAFLD) have an altered gut microbiota composition. Moreover, hepatic DNA methylation may be altered in the state of NAFLD. Using a fecal microbiota transplantation (FMT) intervention, we aimed to investigate whether a change in gut microbiota composition relates to altered liver DNA methylation in NAFLD. Moreover, we assessed whether plasma metabolite profiles altered by FMT relate to changes in liver DNA methylation. Twenty-one individuals with NAFLD underwent three 8-weekly vegan allogenic donor (n = 10) or autologous (n = 11) FMTs. We obtained hepatic DNA methylation profiles from paired liver biopsies of study participants before and after FMTs. We applied a multi-omics machine learning approach to identify changes in the gut microbiome, peripheral blood metabolome and liver DNA methylome, and analyzed cross-omics correlations. Vegan allogenic donor FMT compared to autologous FMT induced distinct differential changes in I) gut microbiota profiles, including increased abundance of Eubacterium siraeum and potential probiotic Blautia wexlerae; II) plasma metabolites, including altered levels of phenylacetylcarnitine (PAC) and phenylacetylglutamine (PAG) both from gut-derived phenylacetic acid, and of several choline-derived long-chain acylcholines; and III) hepatic DNA methylation profiles, most importantly in Threonyl-TRNA Synthetase 1 (TARS) and Zinc finger protein 57 (ZFP57). Multi-omics analysis showed that Gemmiger formicillis and Firmicutes bacterium_CAG_170 positively correlated with both PAC and PAG. E siraeum negatively correlated with DNA methylation of cg16885113 in ZFP57. Alterations in gut microbiota composition by FMT caused widespread changes in plasma metabolites (e.g. PAC, PAG, and choline-derived metabolites) and liver DNA methylation profiles in individuals with NAFLD. These results indicate that FMTs might induce metaorganismal pathway changes, from the gut bacteria to the liver.
Targeting β-catenin and PD-L1 simultaneously by a racemic supramolecular peptide for the potent immunotherapy of hepatocellular carcinoma
Authors: Zhengjun Zhou, Xiao Li, Guang Yang, Jingmei Wang, Baohua Li, Yinong Huang, Jin Yan, Kaishan Tao
Journal: Theranostics (2023)

Objective:The low clinical utility of immune checkpoint inhibitors (ICIs) against PD-1 or PD-L1 has recently been associated with the activation of the Wnt/β-catenin signaling pathway in hepatocellular carcinoma (HCC), which promotes tumor immune escape and resistance to anti-PD-1/PD-L1 therapy.Hence, we aimed to fabricate a supramolecular peptide which could target the Wnt/β-catenin signaling pathway coupled with ICIs blockage therapy for optimizing HCC immunotherapy.Methods: A racemic spherical supramolecular peptide termed sBBI&PDP nanoparticle was constructed by hierarchical self-assembly, comprising an L-enantiomeric peptide as an inhibitor of BCL9 and β-catenin (sBBI) and a D-enantiomeric peptide as an inhibitor of PD-1/PD-L1 (PDP).Results: sBBI&PDP nanoparticle potently suppressed the hyperactivated Wnt/β-catenin signaling pathway in vitro and in vivo, while blocking endogenous PD-L1 effectively.Furthermore, sBBI&PDP increased the infiltration and action of CD8 + T cells at tumor sites.Notably, compared with the original sBBI and commercial Anti-PD-L1 inhibitors, the designed sBBI&PDP showed stronger antitumor efficacy in an orthotopic homograft mice model of HCC and a PDX HCC model in Hu-PBMC-NSG mice.Moreover, sBBI&PDP possessed a favorable biosafety profile. Conclusion:The successful implementation of this strategy could revitalize ICIs blockage therapy and promote the discovery of artificial peptides for HCC immunotherapy.
Abstract 11559: Prognostic Significance of Senescence-Associated Secretory Phenotype (SASP) Biomarkers in Heart Failure (HF)
Authors: Chenao Qian, Payman Zamani, Oday Salman, Qasim Jehangir, Jordana Cohen, Kushan L Gunawardhana, Danielle Greenawalt, Lei Zhao, Ching-Pin Chang, David A Gordon, Francisco Ramirez-Valle, Thomas P Cappola, Julio A Chirinos
Journal: Circulation (2022)

Background: Cell senescence is involved in various age-related pathologies, including HF. The SASP is a characteristic secretory phenotype from senescent cells. We aimed to assess the prognostic significance of the SASP assessed by a combination of plasma protein biomarkers in human HF. Methods: We measured 25 known SASP associated proteins among 2248 Penn HF Study (PHFS) participants using the SomaScan V4 assay. Factor analysis was used to extract the common variance among these proteins. We assessed the relationship between factor scores and: (1) All-cause death; (2) The composite of death or heart failure hospital admission (DHFA). Hazard ratios (HR) were standardized (per unit increase in z score) to facilitate comparisons. Results: Two SASP factors were identified. The levels of both factors did not differ between HF with reduced EF (n=1761) and HF with preserved EF (n=253). Both factors were associated with the risk of death (Factor 1: HR 1.43 [95%CI, 1.32-1.54]; P&lt;0.0001; Factor 2: HR 1.63 [95%CI, 1.54-1.72]; P&lt;0.0001; Figure 1A ) and DHFA (Factor 1: HR 1.36 [95%CI, 1.29-1.43]; P&lt;0.0001; Factor 2: HR 1.32 [95%CI, 1.26-1.38]; P&lt;0.0001; Figure 1B ). After adjustment for the MAGGIC score and NTproBNP levels, both factors remained associated with death (Factor 1: HR 1.14 [95%CI, 1.03-1.26]; P=0.008; Factor 2: HR 1.47 [95%CI, 1.34-1.61]; P&lt;0.0001; Figure 2A ) and DHFA (Factor 1: HR 1.10; [95%CI, 1.03-1,18]; P=0.004; Factor 2: HR 1.09 [95%CI, 1.02-1.17]; P=0.012; Figure 2B ). Conclusion: Increased SASP components are independently associated with adverse outcomes in HF. Further study is needed to assess whether SASP components are suitable therapeutic targets in heart failure.
Abstract 11396: Early-Onset Recurrent Malignant Arrhythmias in a Child With Hypertrophic Cardiomyopathy
Authors: Isabel Monereo Moreno, CARMEN CARRERAS BLESA, María Ángeles Tejero Hernández, Maria del Mar Rodriguez Vazquez del Rey, Blanca Alexandra Molina Cuevas, Jose Manuel Garrido, Jaime Casares Mediavilla, Marta Yagüe Martín, Rosa Macías, Juan Jimenez-Jaimez, Francesca Perin
Journal: Circulation (2022)

Case presentation: A male newborn was diagnosed with severe hypertrophic cardiomyopathy (HCM) because of a heart murmur. A genetic test identified the previously described pathogenic variant Arg719Trp in MHY7, which was not present in the parents. An additional variant in KCNE2, Ile57Thr, considered as a risk factor for acquired long QT, was found in the patient. Corrected QT interval was normal. At age 3, the child suffered cardiac arrest from which he was successfully defibrillated. Maximal wall thickness was 20 mm (z-score +18). With the patient weighing 18 kg, a subcutaneous implantable cardioverter defibrillator (s-ICD) was implanted with the two-incision technique and nadolol 2 mg/kg/day was started. After 3 appropriate ICD therapies in the following 3 months, amiodarone was associated to betablockers, with no QT prolongation. He suffered 8 more ventricular fibrillation-terminating ICD shocks in the following year, prompting the indication of thoracoscopic bilateral cardiac sympathectomy denervation (BCSD) and referring him for heart transplant evaluation. Following BCSD he was symptom free for 6 months, after which he presented with a prolonged cardiac arrest, needing sedation, 4 ICD shocks and external defibrillation to recover consciousness. After experiencing another electrical storm in the following month, he underwent successful cardiac transplantation at age 5. Discussion: This clinical case is noteworthy for different reasons. First of all, even if Arg719Trp mutation in MHY7 has been associated with full penetrance and early expressivity of HCM (mean age at diagnosis 24 years), the child presented with an extremely rare early-onset of recurrent fatal arrhythmias. The pathogenicity of the associated KNCE2 variant, Ile57Thr, has not yet been elucidated but it has been suggested to confer proarrhythmic susceptibility in the presence of other environmental or genetic risk factors. Another worth-mentioning clinical aspect is that s-ICD proved to be a safe and effective therapy in a child weighing much less than 30 kg. In this case in which heart transplant could not be avoided due to life-threatening arrhythmias, the benefit of the preservation of the central venous circulation with the absence of intravascular leads cannot be overstated.
Abstract 11419: Prognostic Value of Vagal Dysautonomia in Patients With Chagas Disease: 14-year Results of a Population Cohort of the Elderly
Authors: Diego N Moraes, Bruno R Nascimento, Antonio L Ribeiro
Journal: Circulation (2022)

Introduction: The cardiac form is the main responsible for morbidity and mortality of Chagas disease (ChD), given its prevalence and unpredictable clinical evolution. A great part of ChD mortality occurs due to sudden ventricular arrhythmias, and the frequently observed autonomic dysfunction may be associated with unfavorable outcomes. We aimed to evaluate the predictive value of autonomic dysfunction indexes in ChD patients. Methods: The Bambuí Study of Aging is a prospective cohort of residents ≥60 years at study onset (1997), living in the southeastern Brazilian city of Bambuí (15,000 inhabitants). Consented participants underwent annual follow-up visits, and death certificates were tracked. For assessment of respiratory sinus arrhythmia (E:I ratio), patients were instructed to breathe deeply in a 10-second cycle (5 inhales and 5 exhales) while ECG was recorded. Heart rate variability indices (SDRR (standard deviation of adjacent RR intervals) and RMSSD (square root of the mean of the sum of squares of the differences between adjacent RR intervals)) were calculated using a computer algorithm, supervised by an independent cardiologist blinded to clinical data. Multivariable regression was performed to access the prognostic value of autonomic dysfunction indexes, expressed as tertiles, for all-cause mortality, after adjustment for demographic, clinical and ECG variables. Results: From 1,742 qualifying residents, 1,606 were enrolled, being 557 with positive ChD serology. Among these, mean age was 68 (64-74) years, and 32.5% were men. The most frequent ECG abnormality was right bundle branch block (23.2%). In 14 years, loss-to-follow-up was 7.9% and overall mortality was 51.9%. At total 321 ChD patients had valid autonomic indexes measurements. In univariate analyses, measurements of autonomic function predicted all-cause death: E:I ratio (HR: 1.20 (95% CI 1.09-1.33)), SDRR (HR: 1.26 (95% CI 1.14-1.40)) and RMSSD (HR: 1.12 (1.01-1.23)). After adjustment for sex, age and cardiovascular risk factors, none of these indexes remained as independent predictors of mortality. Conclusions: In a long-term cohort of elderly patients with ChD, abnormalities in autonomic function indexes were not independent predictors of 14-year mortality.
Abstract 11648: ECG-Derived Features Enable Prediction of Sudden Death in Ischemic Cardiomyopathy
Authors: Samuel Ruiperez-Campillo, Brototo Deb, Anojan Selvalingam, Ruibin Feng, Prasanth Ganesan, Fleur V Tjong, Hui Ju Chang, Maarten Z. H. Kolk, Christopher Kowalewski, Sunil K Vasireddi, Jatin Goyal, Albert J Rogers, Paul L Clopton, Sanjiv M Narayan
Journal: Circulation (2022)

Introduction: Low left ventricular ejection fraction (LVEF) is an imperfect predictor of sudden cardiac death (SCD) in patients with ischemic cardiomyopathy. Novel features identified via automated ECG analysis might improve the prediction of sudden cardiac death risk. Hypothesis: We hypothesized that machine learning of the ECG can be used to predict SCD. Methods: We studied 5603 ECG Lead V1 beats in 41 patients (64±10 Y) with coronary disease and LVEF≤40% in steady-state pacing. Patients were randomly allocated to independent training and test cohorts in a 70:30 ratio, repeated K=10-fold. Support vector machines were trained to predict mortality at 3Y from the top 20 features derived from these beats (Fig C). Patient-level predictions were made by computing an ECG score that indicates the proportion of test set beats in that patient computed by the beat-level model to predict SCD. Results: Fig A shows the data flow in the study. Beat-level predictions in the validation (n=1678 Lead I beats) cohorts yielded c-statistics of 0.78 for SCD (95% CI, 0.62-0.91). In multivariable models, c-statistic was 0.87 for SCD (95% CI, 0.76-0.98) (Fig B). Conclusions: Machine learning of the ECG reveals novel predictors of SCD risk in patients with ischemic cardiomyopathy. This tool may improve risk stratification and allocation for ICD therapy beyond LVEF alone.
Abstract 11273: Comparison of Outcome Between Type 2 versus Type 1 Myocardial Infarction: A Systematic Review and Meta-Analysis
Authors: Vikash Jaiswal, Song Peng Ang, Angela Ishak, Yusra Nasir, Jia Ee Chia, Mounika Reddy Vadiyala, Sidra Naz, Kriti Kalra, Akash Jaiswal
Journal: Circulation (2022)

Introduction: Unlike type 1 myocardial infarction (T1MI) which is caused by plaque rupture and erosion, type 2 myocardial infarction (T2MI) is due to the mismatch between supply-demand of oxygen. To date, there were limited studies available and consequently, the outcomes of patients with T1MI compared to T2MI remained inconclusive. Hypothesis: We aimed to compare the outcomes of T1MI and T2MI patients in terms of mortality and adverse cardiovascular outcomes. Methods: We performed a systematic literature search of databases for relevant articles from inception until March 20, 2022. Results: 340,802 patients had T1MI while the remaining 52,855 patients had T2MI. Mean age was similar between both groups (T1MI: 69.4 years, T2MI: 71.8 years) while proportion of female was found to be more higher in T2MI (61% vs 38%). Our analysis revealed that patients with T1MI had a significantly lower odds of all-cause mortality (OR 0.44, 95%CI 0.34 to 0.56, p&lt;0.001), in-hospital mortality (OR 0.63, 95%CI 0.46 to 0.86, p&lt;0.001), 1-year mortality(OR 0.35, 95% CI 0.25 to 0.47, p&lt;0.001) and MACE (OR 0.59, 95% CI 0.39 to 0.91, p=0.02). There was no significant difference in terms of 30-day mortality (OR 0.58, 95% CI 0.25 to 1.36, p=0.21), CV mortality (OR 0.95, 95% CI 0.68 to 1.32, p=0.74), all-cause readmission (OR 0.84, 95% CI 0.62 to 1.14, p=0.26) and readmission due to MI (OR 1.22, 95% CI 0.66 to 2.27, p=0.53) between both groups. Conclusions: Patients with T1MI had favourable outcomes in terms of mortality and MACE compared to that with T2MI patients. Further studies should aim at determining the optimal management strategy for these high-risk patients for better patient outcomes.
Abstract 11223: Left Atrial Volumetric/Mechanical Coupling Index: A Novel Predictor of Clinical Outcomes in Heart Failure With Preserved Ejection Fraction
Authors: Masato Okada, Nobuaki Tanaka, Onishi Toshinari, Katsuomi Iwakura, Masahiro Seo, Takaharu Hayashi, Masamichi Yano, Akito Nakagawa, Yusuke Nakagawa, Shunsuke Tamaki, Takahisa Yamada, Yasumura Yoshio, Yohei Sotomi, Daisaku Nakatani, Shungo Hikoso, Yasushi Sakata
Journal: Circulation (2022)

Background: Left atrial (LA) dysfunction is common in heart failure with preserved ejection fraction (HFpEF). A higher LA volumetric/mechanical coupling index (LACI), calculated as the LA volume index (LAVI) divided by the diastolic late mitral annular velocity (a’), corresponds to weaker atrial mechanical activity for a larger volume index. Recently, the prognostic importance of the LACI has been reported in patients with heart failure with reduced ejection fraction, but data in patients with HFpEF are limited. Purpose: To investigate whether the LACI is associated with prognosis in patients with HFpEF. Methods: An analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 1231 patients hospitalized for acute heart failure (diagnosed by using Framingham criteria) met the inclusion criteria: a left ventricular ejection fraction (LVEF) ≥50% and brain natriuretic peptide ≥100 pg/ml. After excluding patients with persistent atrial fibrillation, we enrolled 508 patients (age, 80±10 years; females, 58.9%; paroxysmal atrial fibrillation, 18.5%) whose LAVI and a’ at discharge were available. Heart failure hospitalizations and cardiovascular deaths were the primary endpoint. Results: There was a weak negative correlation between the LAVI (median 42, interquartile range [IQR] 32-55 ml/m 2 ) and a’ (median 6.9, IQR 5.3-8.6 cm) (r=-0.26, p &lt;0.001). As a result, the overall LACI was 6.28 (IQR 4.11-9.46). During a median follow-up of 729 (IQR 407-1180) days after discharge, 171 patients experienced the primary endpoint. The incidence incrementally increased with the LACI quartile groups (Q1: 22.1%, Q2: 33.1%, Q3: 38.6%, Q4: 40.9%, log-rank p = 0.003). After adjusting for age, gender, body mass index, left ventricular filling pressure, and serum brain natrium peptide levels, the LACI (hazard ratio, 1.18 per quartile increase; 95% confidence interval, 1.00-1.38; p = 0.045) was a significant predictor of the primary endpoint. Conclusions: The LA mechanical activity decreased with enlargement of the left atrium. The LACI was a novel index for predicting clinical outcomes in patients with HFpEF
Abstract 11407: A Novel Electronic Frailty Index as a Predictor of Clinical Outcomes After ST-Elevation Myocardial Infarction in Older Patients
Authors: Rahul V Annabathula, Zachary Pruitt, Katie Withers, David X Zhao, manrique alvarez, Karl Richardson, Maria O Rangel
Journal: Circulation (2022)

Introduction: Adverse outcomes after ST-elevation myocardial infarction (STEMI) are significant in frail patients. Standard metrics of frailty may not be reliable in acute STEMIs. This study aims to assess a novel, health record-based Electronic Frailty Index (eFI) to evaluate clinical outcomes after STEMI. Methods: Single site, retrospective study of 120 STEMI patients aged ≥65 years from 10/2017-1/2021. Data came from the ACC Chest Pain-MI Registry and health record. Patients were grouped as Fit (eFI ≤0.1) and Not Fit (eFI ≥0.1). Analysis included descriptive statistics and binary logistic regression. Primary outcome was mortality; other outcomes included MACE, bleeding complications, resource utilization, and discharge medications. Results: Mean age and standard deviation of the cohort was 75 (±7.49) years; 45 (38%) were female. 89 (74%) were classified as Not Fit (eFI ≥0.1). Individuals in this group had lower systolic blood pressure (SBP) on presentation, longer times to revascularization, and more comorbidities (Table 1). In-hospital mortality was significantly higher in the Not Fit group (19% vs. 3%, p 0.03); no significant difference in other outcomes (Table 2). Binary logistic regression analysis identified only initial SBP as a significant predictor of in-hospital mortality and not eFI. Conclusions: Increasing frailty, as assessed by the eFI, is associated with greater in-hospital mortality after STEMI. This association was driven by lower initial SBP, which is likely a result of decreased physiological reserve associated with frail status. Larger studies may provide better understanding on the use of eFI in risk stratification of STEMI patients.
Abstract 11149: Pretreatment With P2Y12 Inhibitors in ST-Elevation Myocardial Infarction &amp; Systematic Review and Meta-Analysis
Authors: Douglas Mesadri Gewehr, Caroline Dagostin, Rhanderson Cardoso, Taiane B kubrusly, Fernando B Kubrusly, Luiz F Kubrusly
Journal: Circulation (2022)

Background: the practice of pretreatment with oral P 2 Y 12 inhibitors in ST-Elevation Myocardial Infarction (STEMI) remains common; however, its association with improved cardiovascular outcomes is unclear, since no large RCT has addressed this issue. Hypothesis: We aimed to evaluate the association of oral P2Y12 inhibitor pretreatment in STEMI patients with cardiovascular and bleeding outcomes. Methods: PubMed, MEDLINE, Embase, Cochrane, Scopus, Web of Science were systematically searched for studies that compared pretreatment with P 2 Y 12 versus no pretreatment in STEMI, and reported efficacy and safety outcomes. A meta-analysis using a fixed and random effects model was used to calculated outcomes of interest. Heterogeneity was assessed with I 2 statistics. Results: A total of 3 RCTs and 14 observational studies assigning 91,771 patients to either pretreatment (65,598 patients) or no pretreatment (26,171 patients) were included. Follow-up ranged from 7 days to 19 months. The P 2 Y 12 inhibitors included clopidogrel, prasugrel and ticagrelor. At 30 days, P 2 Y 12 pretreatment was associate with lower 30-day mortality (risk ratio [RR], 0.71; 95% CI, 0.56-0.91; p=0.006; I 2 =75%), stent thrombosis (RR, 0.33; 95% CI, 0.12-0.95; p=0.04; I 2 =83%), and major bleeding (RR, 0.81; 95% CI, 0.74-0.90; p&lt;0.0001; I 2 =0%). No difference in the incidence of 30-day myocardial infarction (MI), target vessel revascularization (TVR), MACE (death/MI/TVR), stroke, pre-PCI TIMI 0 flow, and post-PCI TIMI 0-2 flow was observed. Subgroup analysis including only randomized studies indicated no difference in all-cause mortality between groups (RR, 1.49; 95% CI, 0.89-2.52; p=0.13; I 2 =38%). Conclusion: In this study, pretreatment with oral P2Y12 inhibitors among patients with STEMI before cath lab, compared with treatment once coronary anatomy is known, was associated with decreased all-cause mortality and bleeding risk.